The surfactant material which lines the alveolar surface of the lung has been found to contain lipoproteins. The phospholipids of these lipoproteins possess the surface-active properties necessary for normal lung function. The purpose of this research is to identify factors which regulate normal lipid metabolism in the lung. Isolated perfused rat lung will be used to study the pathway of synthesis of lung lipids and specifically the lipoproteins of the surfactant fraction. The dependence of lipid metabolism on carbohydrate metabolism in the lung and the extent to which carbohydrate metabolism regulates surfactant synthesis will be determined. This will be accomplished by studying the effect of experimentally induced diabetes on the synthesis of phospholipids and the concentration of cyclic nucleotides in the lung. Also, the effect of insulin, cyclic nucleotides and agents which alter endogenous cyclic nucleotide concentrations will be studied in the perfused lung. The significance of glucose as an energy source and as a precursor of lung fatty acids will be investigated as well as the significance of the substantial lactate production by the lung. Other studies will be directed toward determining the role of phosphatidylglycerol found in surfactant material and the subcellular site of the synthesis of the disaturated phospholipids of the surfactant. The precursor-product relationship of the phospholipis and their apoproteins of the lamellar bodies and the same components of the secreted surfactant material will be investigated. A study of the effect of cholesterol levels on the metabolism of cholesterol in the lung and on surfactant production will be determined. Development of methodology for the isolation of type II pneumocytes for use in these studies will continue.